Brain edema is a major complication and cause of death following a stroke. The development of ischemic brain edema is related to an increase in the sodium content of the ischemic tissue; however, the mechanisms that lead to this accumulation of sodium are unknown. Previous work from our laboratory has established that sodium crosses the blood-brain barrier by means of specific transport systems which are responsible for secretion of fluid from blood to brain. We postulate that ischemic edema results, in part, from reduced clearance of this secreted fluid. Inhibition of sodium transport across the blood-brain barrier by pharmacologic agents could, therefore, provide a way to limit brain edema formation. The goal is to determine the role of sodium transport at the blood-brain barrier in the development of ischemic brain edema. Two models of cerebral ischemia will be compared: partial unilateral ischemia and complete bilateral ischemia with reperfusion. At various times after these insults, we will quantitate and correlate regional brain edema, tissue content of sodium and potassium, cerebral blood flow rate, brain blood volume, blood-brain barrier integrity, and the rate of transport of sodium from blood to brain. The relationship between blood flow, amount of edema, and rate of sodium uptake will be determined. These studies will improve our understanding of ischemic brain edema and this could ultimately lead to more effective therapy for this important complication of stroke.